The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A)delta-subunit-containing receptors.
The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A)delta-subunit-containing receptors.
复制标题
THIP（加波沙朵）对睡眠和清醒的脑电图影响是由含有 GABA(A)δ 亚基的受体介导的。
DOI：
10.1111/j.1460-9568.2007.05455.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Tobler,Irene
中科院分区：
文献类型：
--
作者：
Winsky-Sommerer,Raphaelle;Vyazovskiy,VladyslavV;Homanics,GreggE;Tobler,Irene
THIP (4,5,6,7‐tetrahydroisoxazolo‐[5,4‐c]pyridine‐3‐ol, Gaboxadol) is a selective γ‐aminobutyric acid (GABA)Aagonist, actingin vitrowith high potency and efficacy at the extrasynaptic GABAAδ‐containing receptors. THIP was suggested to be a potential hypnotic to treat insomnia, and it is currently in clinical trial. Here we assessed whether the GABAAδ‐containing receptors mediatein vivothe effect of THIP on sleep and the sleep electroencephalogram (EEG). We performed EEG recordings in a mouse model deficient in the GABAAδ‐subunit gene (δ–/–mice) and in wild‐type littermate controls. THIP (4 and 6 mg/kg intraperitoneally) induced an abnormal EEG pattern, resulting in dramatic changes in the waking and non‐rapid eye movement (NREM) sleep EEG spectra in wild‐type mice. Indeed, a massive increase in EEG power lasting 2–3 h occurred in both the frontal and parietal derivation, especially in frequencies below 6 Hz. All effects were more prominent in the frontal EEG. Furthermore, the highest dose of THIP lengthened REM sleep latency and suppressed REM sleep. In contrast, vigilance states and sleep latencies were not affected in δ–/–mice. Moreover, only minor changes were observed in the NREM sleep EEG spectrum after THIP injection in the δ‐subunit‐deficient mice. The present findings do not indicate a sleep‐promoting effect of THIP in mice, which is in accordance with a previous report in this species. Moreover, our resultsin vivodemonstrate that THIP acts preferentially at GABAAreceptors containing the δ‐subunit.
